The Nature Of Chagas Disease

In Latin America, 18-20 million people are infected with T. cruzi resulting in up to 50,000 fatalities per year.[1] Chagas' disease is endemic in more than 20 counties with 100 million people at risk. It is by far the most serious parasitic infection in the region with an estimated economic burden of $8 billion per year. There is a close association between poverty and the disease because the reduviid bug that transmits the parasite is usually restricted to poor-quality housing. Most individuals are infected while sleeping, when parasites are deposited on their skin as the bug defecates during a bloodmeal. The parasites then penetrate the skin, typically via the bite wound or other lesion (Fig. 1). Transmission can also occur congenitally (5-10% of children born to infected mothers are themselves infected) or by blood transfusion. This latter route is increasingly recognized as a potential problem in the United States where there are estimated to be 100,000 infected individuals that have migrated from endemic areas.

In humans, Chagas' disease has three stages. The initial acute stage is characterized by a high parasitemia and a range of symptoms that can last for 4-8 weeks. Although the symptoms are usually mild, there can be a 5% fatality rate in children, often because of acute myocarditis or meningoencephalitis. The disease then subsides and most individuals are asymptomatic for the rest of their lives. However, they remain infectious and can serve as a reservoir. In approximately 30% of cases the disease develops into the chronic form, often many years after the initial infection. Premature and progressive heart disease is the most common clinical manifestation, and prognosis for these individuals is poor. Other serious symptoms that can be associated with chronic disease include swelling of the esophagus and colon (the so-called megasyndromes) and abnormalities of the central nervous system. Reactivation of T. cruzi infection in HIV carriers has also been recognized as an increasing problem. Most patients identified with dual infections have been found to display neurological dysfunction and/or heart lesions.

Pathology in Chagas' disease is mainly a consequence of interactions between the parasite and the host immune system. T. cruzi elicits polyclonal lymphocyte activation, a type of response common in many viral, bacterial, and parasitic diseases and which is thought to constitute a nonspecific immune evasion strategy. This has also been linked with the immunosuppression and pathology associated with the chronic form of Chagas' disease. Geographical variations in the percentage of infected people who go on to develop chronic disease has hinted that the spectrum of symptoms may reflect the genotypic diversity of the parasite (below) rather than differences in host genetic background, although this remains controversial.

There has been a major debate within the Chagas' disease research community about the factors responsible for triggering the development of the chronic pathology.[2] Some have argued that the continued presence of the parasite is required, whereas others consider that the disease is an autoimmune condition. There is now strong evidence, at least in a mouse model, that the continued presence of the parasite is both sufficient and necessary to promote chronic disease pathology.[3] This has important